CCAAT/enhancer-binding Proteins β(C/EBPβ) Up-regulates Transcription Of BRCA1 Gene In Human Breast Cancer Cells

Objective:To evaluate the variation of BRCA1 promoter's DNA sequences and investigate whether or how the transcription factor C/EBPβand CBP/P300 regulate BRCA1 transcription.Methods:Collect peripheral blood samples of breast benign diseases,sporadic breast cancers and hereditary breast cancers,detect the variation of BRCA1 promoter sequences using DHPLC and DNA Sequence Analysis.Transfect C/EBPβand CBP/P300 plasmids into breast cancer cell lines to see whether they combine to the BRCA1 promoter,regulate its transcription and affect its mRNA or protein level.Results:Though PCR to check 600 BRCA1 promoter DNA sequences,we found only one C＞G mutation in 1492bp before the N-terminal in a hereditary breast cancer patient.BRCA1 promoter activity can be upgrade by C/EBPβthough Luciferase assay.Chromatin immunoprecipitation(ChIP) determined C/EBPβcan bind to BRCA1 promoter,RT-PCR and Western-blot suggested C/EBPβcan increase BRCA1 mRNA and protein level.CBP/P300 can upgrade BRCA1 promoter activity and increase BRCA1 mRNA level only in MCF7 cell which is ER positive breast cancer cell.We found E2 and ERαare positive to BRCA1 transcription;E2 can stimulate ERαand CBP/P300 to form a transcription complex binding to BRCA1 promoter.The histone protein can be acetylated by E2.Conclusion:BRCA1 promoter sequences are conservative in Chinese population. The transcriptional factor C/EBPβcan activate the transcription of BRCA1 gene.In the stimulation of E2,ERαand CBP/P300 can form a transcription complex and bind to BRCA1 promoter,though acetylating the core histone protein,increase BRCA1 transcription.